DESCRIPTION (adapted from the application) The non-invasive estimation of beta-cells mass (BCM) by imaging would have significant impact in managing clinical diabetes mellitus (DM), pancreas and/or islet cell transplantation and the understanding of the pathogenesis of DM. Unfortunately, such non-invasive techniques are currently not available. The overall goal of this proposal is to test whether islet cell specific imaging by nuclear and nuclear magnetic resonance technology is feasible, accurate and predictive of BCM in normal and diabetic states. Based on our prior experience in target specific imaging we hypothesize that certain imaging parameters (e.g., percent injected dose/g tissue, morphologic signal changes or signal intensity changes) will correlate with BCM using beta-cell target-specific imaging ligands. In preliminary experiments we have tested 2 anti-beta-cell IgM monoclonal antibodies (IC2, R2D6) in isolated islet experiments as well as in vivo in a mouse model. Our results show that highly specific binding and accumulation to beta-cells occurs following IV administration with virtually no binding to exocrine pancreas nor stromal tissues, setting an ideal stage for the proposed work. Given the ability to spatially encode the imaging signal, it should thus be feasible to measure BCM. The proposed experiments are a logical extension of the feasibility experiments, and if successful, a transition of this research would be tested in clinical trials.